Efficacy and Safety of Anti-Interleukin-5 Therapy in Patients with Asthma: A Systematic Review and Meta-Analysis

BackgroundRecent trials have assessed the efficacy and safety of novel monoclonal antibodies such as reslizumab and benralizumab. However, the overall efficacy and safety anti—interleukin (IL) 5 treatment in asthma have not been thoroughly assessed.MethodsRandomized controlled trials (RCTs) of anti-IL-5 treatment on patients with asthma published up to October 2016 in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) that reported pulmonary function, quality of life scores, asthmatic exacerbation rate, blood and sputum eosinophil counts, short-acting β-agonist (SABA) rescue use, and adverse events were included. The pooled mean difference, and relative risks (RR), and 95% confidence intervals (CIs) were calculated using random-effects models.ResultsTwenty studies involving 7100 patients were identified. Pooled analysis revealed significant improvements in FEV1 (first second forced expiratory volume) (MD = 0.09, 95% CI: 0.06–0.12, I2 = 10%), FEV1% (MD = 3.75, 95% CI: 1.66–5.83, I2 = 19%), Asthma Quality of Life Questionnaire (AQLQ) score (MD = 0.22, 95% CI: 0.15–0.30, I2 = 0%), decreased blood, sputum eosinophils and asthmatic exacerbation (RR = 0.66, 95% CI: 0.59–0.73, I2 = 51%); peak expiratory flow (PEF) (MD = 5.45, 95% CI: -2.83–13.72, I2 = 0%), histamine PC20 (MD = -0.62, 95% CI: -1.92–0.68, I2 = 0%) or SABA rescue use (MD = -0.11, 95% CI: -0.3–0.07, I2 = 30%) were unaffected; adverse events were not increased (RR = 0.93, 95% CI: 0.89–0.98, I2 = 46%). No publication bias was observed (Egger's P = 0.78).ConclusionsAnti-interleukin 5 monoclonal therapies for asthma could be safe for slightly improving FEV1 (or FEV1% of predicted value), quality of life, and reducing exacerbations risk and blood and sputum eosinophils, but have no significant effect on PEF, histamine PC20, and SABA rescue use. Further trials required to establish to clarify the optimal antibody for different patients.背景 近期已有多项试验评估了瑞利珠单抗（reslizumab）、贝纳利珠单抗（benralizumab）等新型单克隆抗体的疗效与安全性，但目前尚未对哮喘患者接受抗白细胞介素5（interleukin 5, IL-5）治疗的整体疗效与安全性进行全面评估。 方法 本研究纳入了截至2016年10月发表于PubMed、Embase及Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials, CENTRAL）的、针对哮喘患者的抗IL-5治疗随机对照试验（randomized controlled trial, RCT），这些试验需报告肺功能、生活质量评分、哮喘急性加重率、血液及痰液嗜酸性粒细胞计数、短效β受体激动剂（short-acting β-agonist, SABA）急救使用情况以及不良事件。本研究采用随机效应模型计算合并均数差、相对危险度（relative risk, RR）及95%置信区间（confidence interval, CI）。 结果 本研究共纳入20项研究，涉及7100例患者。合并分析结果显示，第一秒用力呼气容积（forced expiratory volume in one second, FEV1）（均数差（mean difference, MD）=0.09，95%置信区间：0.06~0.12，I²=10%）、FEV1占预计值百分比（FEV1%）（MD=3.75，95%CI：1.66~5.83，I²=19%）、哮喘生活质量问卷（Asthma Quality of Life Questionnaire, AQLQ）评分（MD=0.22，95%CI：0.15~0.30，I²=0%）均显著改善，血液及痰液嗜酸性粒细胞水平降低，哮喘急性加重风险下降（RR=0.66，95%CI：0.59~0.73，I²=51%）；而峰值呼气流速（peak expiratory flow, PEF）（MD=5.45，95%CI：-2.83~13.72，I²=0%）、组胺PC20（MD=-0.62，95%CI：-1.92~0.68，I²=0%）及SABA急救使用情况（MD=-0.11，95%CI：-0.3~0.07，I²=30%）无显著变化；不良事件发生率未升高（RR=0.93，95%CI：0.89~0.98，I²=46%）。未观察到发表偏倚（Egger检验P=0.78）。 结论 哮喘患者接受抗IL-5单克隆抗体治疗安全性良好，可轻度改善FEV1（或FEV1占预计值百分比）与生活质量，降低哮喘急性加重风险及血液、痰液嗜酸性粒细胞水平，但对PEF、组胺PC20及SABA急救使用无显著影响。未来需开展更多试验以明确适用于不同患者的最优抗体。